U.S. patent number 7,098,452 [Application Number 10/778,424] was granted by the patent office on 2006-08-29 for atmospheric pressure charged particle discriminator for mass spectrometry.
This patent grant is currently assigned to MDS Sciex. Invention is credited to Thomas R. Covey, Bradley Schneider.
United States Patent |
7,098,452 |
Schneider , et al. |
August 29, 2006 |
Atmospheric pressure charged particle discriminator for mass
spectrometry
Abstract
An apparatus and method for performing mass spectroscopy uses an
ion interface to provide the function of removing undesirable
particulates from an ion stream from an atmospheric pressure ion
source, such as an electrospray source or a MALDI source, before
the ion stream enters a vacuum chamber containing the mass
spectrometer. The ion interface includes an entrance cell with a
bore that may be heated for desolvating charged droplets when the
ion source is an electrospray source, and a particle discrimination
cell with a bore disposed downstream of the bore of the entrance
cell and before an aperture leading to the vacuum chamber. The
particle discrimination cell creates gas dynamic and electric field
conditions that enables separation of undesirable charged
particulates from the ion stream.
Inventors: |
Schneider; Bradley (Bradford,
CA), Covey; Thomas R. (Richmond Hill, CA) |
Assignee: |
MDS Sciex (Concord,
CA)
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Family
ID: |
33551246 |
Appl.
No.: |
10/778,424 |
Filed: |
February 13, 2004 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20040217280 A1 |
Nov 4, 2004 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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60447655 |
Feb 14, 2003 |
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Current U.S.
Class: |
250/288 |
Current CPC
Class: |
H01J
49/044 (20130101); H01J 49/06 (20130101) |
Current International
Class: |
H01J
49/04 (20060101) |
Field of
Search: |
;250/288 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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0 622 830 |
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Nov 1994 |
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EP |
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1 193 730 |
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Apr 2002 |
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EP |
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2 324 906 |
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Nov 1998 |
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GB |
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11-108894 |
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Apr 1999 |
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JP |
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2000-55880 |
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Feb 2000 |
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JP |
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Other References
Zubarev et al., Electron Capture Dissociation of Multiply Charged
Protein Cations. A Nonergodic Process: 1998 American Chemical
Society, 120, 3265-3266. cited by other .
Lee et al., Thermally Assisted Electrospray Interface for Liquid
Chromatography/Mass Spectrometry; Rapid Communications in Mass
Spectrometry, vol. 6, 727-733 (1992). cited by other .
Herron et al., Reactions of Polyatomic Dianions with Cations in the
Paul Trap, Rapid Communications in Mass Spectrometry, vol. 10,
277-281 (1996). cited by other .
Schneider et al., Atmospheric Pressure Charged Particle
Discrimination Interface for Low Flow Rate ESI-MS -ASMS Abstract.
cited by other .
Schneider et al., Particle Discriminator Interface for Nanoflow
ESI-MS 2003 American Society for Mass Spectrometry. cited by other
.
Niessen, "Advances in instrumentation in liquid chromatography-mass
spectrometry and related liquid-introduction techniques," Journal
of Chromatography A. 794 (1998) pp. 407-435. cited by
other.
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Primary Examiner: Berman; Jack I.
Attorney, Agent or Firm: Leydig, Voit & Mayer, Ltd.
Parent Case Text
CROSS-REFERENCE TO RELATED PATENT APPLICATION
This application claims the priority of U.S. Provisional
Application 60/447,655, filed Feb. 14, 2003.
Claims
What is claimed is:
1. A system for ion mass spectroscopy comprising: an ion source
disposed in atmospheric pressure; a mass spectrometer; a vacuum
chamber containing the mass spectrometer; an ion interface disposed
between the ion source and the vacuum chamber for introducing ions
generated by the ion source into the vacuum chamber for analysis by
the mass spectrometer, the ion interface comprising an entrance
cell and a particle discrimination cell, the entrance cell having a
bore disposed to receive output of the ion source to form an ion
stream containing analyte ions and undesirable particulates, the
particle discrimination cell having a bore disposed downstream of
the bore of the entrance cell and upstream of an aperture in a
partition separating atmospheric pressure from the vacuum chamber,
the bore of the particle discrimination cell having a central zone
and a discrimination zone surrounding the central zone and being
sized larger than the bore of the desolvation cell to cause
formation of eddies in the discrimination zone when the ion stream
flows from the bore of the entrance cell into the bore of the
particle discrimination cell, the particle discrimination cell
having a voltage applied thereto for generating a discrimination
electric field in the bore thereof, whereby the discrimination
electric field and the formation of eddies in the particle
discrimination cell together provide an effect of removing a
portion of the undesirable particulates from the ion stream prior
to entering the vacuum chamber through the aperture of the
partition.
2. A system for ion mass spectroscopy as in claim 1, wherein the
ion interface includes a heater for heating the entrance cell.
3. A system for ion mass spectrometer as in claim 1, wherein the
ion interface further includes a curtain plate disposed downstream
of the ion source for providing a curtain gas flow in a reverse
direction to the output of the ion source.
4. A system for ion mass spectroscopy as in claim 1, wherein the
ion source is an electrospray source generating a spray of charged
droplets, and wherein ion interface includes a heater for heating
the entrance cell for drying the spray as the charged droplets pass
through the bore of the entrance cell.
5. A system for ion mass spectroscopy as in claim 4, further
including a curtain plate disposed between the electrospray source
and the entrance cell for providing a curtain gas flow in a reverse
direction to the spray.
6. A system for ion mass spectroscopy as in claim 1, wherein the
ion source is a matrix-assisted laser desorption/ionization (MALDI)
source generating a plume of ions.
7. A system for ion mass spectroscopy as in claim 6, further
including a curtain plate disposed between the MALDI source and the
entrance cell for providing a curtain gas flow in a reverse
direction to the plume.
8. A system for ion mass spectroscopy as in claim 1, wherein the
bore of the entrance cell has a diameter between 0.75-3 mm and the
bore of the particle discrimination chamber has a diameter between
2-20 mm.
9. A system for ion mass spectroscopy as in claim 1, wherein the
ion interface further includes a blocking member located inside the
bore of the particle discrimination cell.
10. A system for ion mass spectroscopy as in claim 9, wherein the
blocking member is located on an axis of the bore of the particle
discrimination cell.
11. A method of interfacing an ion source operating in atmospheric
pressure with a mass spectrometer contained in a vacuum chamber,
comprising: directing output of the ion source into a bore of an
entrance cell to generate an ion stream, the ion stream containing
analyte ions and undesirable particulates, and passing the ion
stream into a bore of a discrimination cell disposed downstream of
the desolvation cell and upstream of an aperture of a partition
separating atmospheric pressure from the vacuum chamber, the bore
of the discrimination cell having a central zone and a
discrimination zone surrounding the central zone and being sized
greater than the bore of the desolvation cell to cause formation of
eddies in the discrimination zone when the ion stream flows from
the desolvation cell into the discrimination cell; and applying a
voltage to the discrimination cell to generate a discrimination
electric field in the bore of the discrimination cell, whereby the
discrimination electric field and generation of eddies in the
discrimination cell together provide an effect of removing a
portion of the undesirable particulates from the ion stream prior
to entering the vacuum chamber through the aperture of the
partition.
12. A method as in claim 11, wherein the ion source is an
electrospray source for generating a spray of charged droplets, the
method further including the step of heating the entrance cell for
drying the spray as the charged droplets pass through the bore of
the entrance cell.
13. A method as in claim 12, further including the step of
providing a flow of gas in a reverse direction of the spray to
assist desolvation of the spray.
14. A method as in claim 11, wherein the ion source is a
matrix-assisted laser desorption/ionization (MALDI) source.
15. An ion interface for interfacing an ion source disposed in
atmosphere pressure and a mass spectrometer contained in a vacuum
chamber, comprising: an entrance cell disposed to receive output of
the ion source to form an ion stream containing analyte ions and
undesirable particulates; and a particle discrimination cell having
a bore disposed downstream of the bore of the entrance cell and
upstream of an aperture in a partition separating atmospheric
pressure from the vacuum chamber, the bore of the particle
discrimination cell having a central zone and a discrimination zone
surrounding the central zone and being sized larger than the bore
of the desolvation cell to cause formation of eddies in the
discrimination zone when the ion stream flows from the bore of the
entrance cell into the bore of the particle discrimination cell,
the particle discrimination cell having a voltage applied thereto
for generating a discrimination electric field in the bore thereof,
whereby the discrimination electric field and the formation of
eddies in the particle discrimination cell together provide an
effect of removing a portion of the undesirable particulates from
the ion stream prior to entering the vacuum chamber through the
aperture of the partition.
16. An ion interface as in claim 15, further including a heater for
heating the entrance cell.
17. A ion interface as in claim 15, further including a curtain
plate disposed downstream of the ion source for providing a curtain
gas flow in a reverse direction to the output of the ion
source.
18. An ion interface as in claim 15, wherein the ion source is an
electrospray source generating a spray of charged droplets, and
wherein the ion interface includes a heater for heating the
entrance cell for drying the spray as the charged droplets pass
through the bore of the entrance cell.
19. An ion interface as in claim 18, further including a curtain
plate disposed between the electrospray source and the entrance
cell for providing a curtain gas flow in a reverse direction to the
spray.
20. An ion interface as in claim 15, wherein the ion source is a
matrix-assisted laser desorption/ionization (MALDI) source.
21. An ion interface as in claim 15, wherein the bore of the
entrance cell has a diameter between 0.75-3 mm and the bore of the
particle discrimination chamber has a diameter between 2 to 20
mm.
22. An ion interface as in claim 15, wherein the ion interface
further includes a blocking member located inside the bore of the
particle discrimination cell.
23. An ion interface as in claim 22, wherein the blocking member is
located on an axis of the bore of the particle discrimination cell.
Description
FIELD OF THE INVENTION
This invention relates to mass spectrometry, and more particularly
to the interface between an atmospheric pressure ion source and low
pressure regions of a mass spectrometer.
BACKGROUND OF THE INVENTION
Samples or analytes for analysis in mass spectrometers are often
ionized in an atmospheric environment, and the ions are then
introduced into a vacuum chamber that contains the mass
spectrometer. An atmospheric pressure ion source provides
advantages in handling of samples, but the introduction of ions
from the ion source into the vacuum chamber often requires a proper
interface disposed between the ion source and the vacuum chamber.
For instance, one common family of ionization techniques includes
electrospray and its derivatives, such as nanospray, which provides
a low flow. In all such techniques, a liquid sample, containing the
desired analyte in a solvent, is caused to form a spray of charged
and neutral droplets at the tip of an electrospray capillary. Once
the spray is produced, the solvent begins to evaporate and is
removed from the droplet, which is a process commonly referred to
as desolvation. Accordingly, an important step in generating ions
is to ensure proper desolvation. The electrospray source is usually
coupled with some means of desolvation in an atmospheric pressure
chamber, where desolvation can be enhanced by heat transfer to the
droplets (radiation, convection) or/and counter-current flow of dry
gas. The spray generally consists of a distribution of droplet
sizes, and subsequently, the degree of desolvation will be
different for each droplet size. Consequently, after desolvation,
there is a size distribution for desolvated particles where there
are large and heavy charged particles that may contaminate the
aperture or conductance limit, thereby preventing the long-term
stable operation of the mass analysis region, and/or introducing
additional noise to the ion detector. This additional source of
noise reduces the signal to nose ratio and thus, the sensitivity of
the mass spectrometer.
The ions and the accompanying solvent molecules (neutrals) and
charged particles, are transferred from the atmospheric pressure
region to the low-pressure chamber of the mass spectrometer.
Generally, the mass spectrometer operates less than 10.sup.-4 Torr
and requires stages of skimmers or apertures to provide step-wise
pressure reduction. Various methods for allowing the ions to enter
while preventing the neutrals from passing into the mass
spectrometer are well known. In U.S. Pat. No. 4,023,398, assigned
to the assignee of the present invention and the contents
incorporated here, as represented in FIG. 9, the mass spectrometer
32 is coupled to atmosphere by the interface region 15. A partition
3 with an entrance aperture 4 is provided to separate the
atmospheric pressure from the first vacuum or lower pressure region
10 of the mass spectrometer 32 and a curtain gas 7 is supplied to
prevent surrounding gases and neutrals 14 from entering the vacuum
regions 10 & 11. The diameter of the entrance aperture 4 is
chosen to limit the gas flow from the atmospheric region in order
to balance the pumping capacity of the first and subsequent vacuum
pumps 12 and 13 in the mass spectrometer region 32. A curtain plate
5 with an orifice 6 is located between the entrance aperture 4 and
the spray 2. The purpose of the curtain plate 5 is to apply a flow
of curtain gas 7 in the reverse direction of the spray 2. The
curtain gas 7 has two functions: to divert the neutrals 14 from
entering the aperture 4 and to desolvate the charge droplets so to
release ions. In this method, charged particulates and heavy
charged droplets that are not fully desolvated and remain as
residual charged droplets may pass through the curtain gas flow and
continue to travel downstream towards the entrance aperture 4.
U.S. Pat. Nos. 4,977,320, and 5,298,744, teach a method whereby a
heated tube made from conductive or non-conductive material is used
for delivering the ions/gas carrier/solvent flow into the
low-pressure chamber. In such a configuration, the heated tube
provides two distinct and separate functions; firstly, due to its
significant resistance to gas flow, the tube configuration, namely
its length and inner diameter, adjusts the gas load on the pumping
system; secondly, the tube can be heated to effect desolvation and
separation of ions from neutrals. With respect to the first
function, this resistance can be provided, while keeping the tube
length constant, to ensure laminar gas flow in the tube and the
widest possible opening for inhaling the ion/gas carrier/solvent
flow. Generally, a wider bore for the tube provides increased gas
flow and hence more load on the pumping system; correspondingly,
reducing the tube length provides less resistance to the gas flow,
so as also to increase the gas flow and load on the pumping system.
These two geometric parameters, bore and length, are obviously
related and can be adjusted to provide the desired flow rate and
flow resistance. The second function is provided by mounting a
heater around the interface tube. The heat provided to the tube
promotes desolvation of the ion flow, and also helps to reduce
contamination of the surface of the tube, thereby reducing memory
effects. An interface of this type is able to work best under
strictly laminar flow conditions, limiting the variability of the
tube length and tube bore. Additionally, the desolvation, which
depends on temperature and residence time (inversely proportional
to gas velocity through the tube) is related to the pumping
requirements. As a rule, it is not possible to optimize all the
desired parameters; in particular, it is desirable to minimize
total mass flow to reduce pumping requirements, on the other hand
to ensure best efficiency for transfer of ions into the mass
spectrometer, a large diameter tube with high mass flow rates is
desirable. In addition, the desolvation of ions is also affected by
the diameter of the tube due to changes in residence time.
U.S. Pat. No. 5,304,798 attempts to satisfy both of these
requirements by teaching a method whereby a chamber has a contoured
passageway to provide both the desolvation function and the
capillary restriction function. The opening of the passageway
adjacent to atmospheric pressure has a wide and long bore while the
opposite end of the passageway, ending within the vacuum chamber,
has a smaller shorter bore. The electrospray source is place in
front of the opening of the wide bore allowing the spray to pass
directly into the passageway. The desolvation is performed within
the wide bore region while the smaller bore provides the mass flow
restriction. The entire spray is passed into the desolvation tube
and any neutral or charged particulates or droplets not fully
desolvated, will pass into the small bore. These particulates or
droplets can accumulate in the small bore, which may cause blockage
or they may pass through the small bore and enter the vacuum
chamber leading to extensive contamination.
U.S. Pat. No. Re. 35,413 describes a desolvation tube and a skimmer
arrangement where the exit of the desolvation tube is positioned
off-axis to the skimmer. Offsetting the axis of the tube from the
orifice of the skimmer is intended to allow the ions to flow
through the orifice while the undesolvated droplets and
particulates impinge upon the skimmer. This method does not take
into consideration that the undesolvated droplets or charged
particles, are not restricted to travel along the axis of the
desolvation tube but follow a distribution across the bore. That
is, this arrangement will only prevent undesolvated droplets and
particulates traveling along the central axis from entering the
orifice. An offset of the desolvation tube will not prevent
droplets and charged particulates aligned with the offset location
from entering the skimmer or to prevent an accumulation from
building up around the orifice. In addition, it is expected that
there would be a reduction of the ion current through the skimmer
as a function of the offset.
In U.S. Pat. No. 5,756,994, a heated entrance chamber is provided,
and is pumped separately. Ions entering this chamber through an
entrance aperture are then sampled through an exit aperture that is
located in the side of the chamber, off any line representing a
linear trajectory from the entrance orifice. The intention of this
off alignment is to prevent the neutral droplets or particles from
entering the exit aperture. Pressure in this heated entrance
chamber is maintained around 100 Torr. To the extent that this is
understood, there is an independent pumping arrangement in the
entrance chamber, and the shape of the chamber is not conducive to
maintaining laminar flow, with the entrance aperture being much
smaller than the cross-section of the main portion of the chamber
itself. It is expected that significant loss of ion current to the
walls of this chamber would occur in addition to obvious
inefficiency of sampling from only one point of cylindrical flow
through the exit aperture.
Another common type of atmospheric pressure ion sources uses the
matrix-assisted laser desorption/ionization (MALDI) technique. In
such a source, photon pulses from a laser strike a target and
desorb ions that are to be measured in the mass spectrometer. The
target material is composed of a low concentration of analyte
molecules, which usually exhibit only moderate photon absorption
per molecule, embedded in a solid or liquid matrix consisting of
small, highly-absorbing species. The sudden influx of energy in the
laser pulse is absorbed by the matrix molecules, causing them to
vaporize and to produce a small supersonic jet of matrix molecules
and ions in which the analyte molecules are entrained. During this
ejection process, some of the energy absorbed by the matrix is
transferred to the analyte molecules, thereby ionizing the analyte
molecules. The plume of ions generated by each laser pulse contains
not only the analyte ions but also charged particulates containing
the matrix material, which may affect the performance of the mass
spectrometer if not removed from the ion stream.
SUMMARY OF THE INVENTION
In view of the forgoing, the present invention provides a system
for preparing ions to be studied by an ion mass spectrometer. The
system has an atmospheric pressure ion source, such as an
electrospray ion source or a MALDI source, a mass spectrometer
contained in a vacuum chamber, and an interface for introducing
ions from the ion source into the vacuum chamber. The interface
includes an entrance cell and a particle discrimination cell.
In an embodiment where the atmospheric pressure ion source is an
electrospray ion source, the entrance cell may function as a
desolvation cell. The electrospray ion source operates in the
atmosphere and provides a spray of charged droplets that contain
ions to be studied. The spray is directed into a heated bore of the
desolvation cell for drying the droplets in the spray to generate
an ion stream, which contains undesirable particulates. A particle
discrimination cell for discriminating against (i.e., removing)
particulates is disposed downstream of the desolvation cell and
before an aperture in a partition that separate the atmospheric
pressure from the vacuum in the vacuum chamber. The particle
discrimination cell has a bore for receiving the ion stream that is
larger than the bore of the desolvation cell and has a central zone
and a discrimination zone surrounding the central zone. Eddies are
formed in the discrimination zone when the ion stream flows into
the bore of the particle discrimination cell. The particle
discrimination cell has a voltage applied thereto for generating a
particle discrimination electric field in its bore. The electric
field and the formation of eddies in the particle discrimination
cell together provide the effect of removing particulates from the
ion stream so that they do not enter the aperture of the
partition.
The present invention also provides a method of interfacing an ion
source that operates in the atmosphere with an ion mass
spectrometer in a vacuum chamber. The ion source may be, for
instance, an electrospray source or a MALDI source. An interface
that contains an entrance cell and a charged particle
discrimination cell is disposed between the atmospheric ion source
and the vacuum chamber. When the ion source is an electrospray
source, the entrance cell is used as a desolvation cell. A spray of
charged ion droplets generated by the ion source is directed into a
heated bore of a desolvation cell for drying the droplets in the
spray to generate an ion stream, which contains undesirable
particulates. The ion stream then is directed through a
discrimination cell that is disposed downstream of the desolvation
cell and upstream of an aperture in a partition that separates the
atmosphere from the vacuum chamber containing the ion mass
spectrometer. The discrimination cell has a bore that is greater
than the bore of the desolvation cell and has a central zone and a
discrimination zone surrounding the central zone. While flowing
from the desolvation cell into the discrimination cell, the ion
stream generates eddies in the discrimination zone of the
discrimination cell. A voltage is applied to the discrimination
cell to generate a discrimination electric field in the bore of the
discrimination cell. The electric field and generation of eddies in
the discrimination cell together provide the effect of removing
undesirable charged particulates from the ion stream so that they
do not enter the aperture of the partition.
BRIEF DESCRIPTION OF THE DRAWINGS
While the appended claims set forth the features of the present
invention with particularity, the invention, together with its
objects and advantages, may be best understood from the following
detailed description taken in conjunction with the accompanying
drawings, of which:
FIG. 1 is a schematic view of the charged particle discriminator in
accordance with the present invention;
FIG. 2 is a schematic view of another charge particle discriminator
in accordance with the present invention;
FIG. 3 is a diagrammatic view of the gas flow streamlines of the
charge particle discriminator in accordance with the present
invention;
FIG. 4 is a diagrammatic view of the electric field of the charge
particle discriminator in accordance with the present
invention;
FIG. 5 is representation of the results from a charge particle
discriminator of FIG. 1;
FIG. 6 is a schematic view of yet another charge particle
discriminator in accordance with the present invention;
FIG. 7 is another diagrammatic view of the gas flow streamlines of
the charge particle discriminator in accordance with the present
invention;
FIGS. 8A, 8B & 8C are schematic views of spacers defining the
charge particle discriminator regions in accordance with the
present invention; and
FIG. 9 is a schematic view of conventional prior art atmospheric
pressure interfaces.
DETAILS OF THE EXEMPLIFYING EMBODIMENTS
Referring now to the drawings, FIG. 1 is an illustration according
to one embodiment of the present invention, which shows an
atmospheric pressure interface generally indicated by 16. The
interface 16 is positioned between an ion source 1 and the mass
spectrometer 32, the interface 16 comprising of at least one
interface cell, described as follows. Ions from the ion source 1
pass into the mass spectrometer 32 comprising of vacuum chambers 10
and 11 through apertures 4 and 9, respectively. The pressure in
each of the vacuum chambers 10 and 11 is step-wise reduced by
vacuum pumps 12 and 13, respectively. The aperture 9 mounted in the
partition 8 between the vacuum stages restricts neutral gas
conductance from one pumping stage to the next while the aperture 4
mounted in the partition 3 restricts the flow of gas from
atmosphere into the vacuum chamber 10. The pressure between the
aperture 4 and the ion source 1 is typically at or near atmospheric
pressure.
The ion source 1 can be a single or a multiple of the many known
types of ion sources depending on the type of sample to be
analyzed. For instance, the ion source may be an electrospray or
ion spray device, a corona discharge needle, a plasma ion source,
an electron impact or chemical ionization source, a photo
ionization source, a MALDI source, or any multiple combinations of
the above. Other desired types of ion sources may be used, and the
ion source may operate at atmospheric pressure, above atmospheric
pressure, near atmospheric pressure, or in vacuum. Generally, the
pressure in the ion source is greater than the pressure downstream
in the mass spectrometer 32. The ion source 1 produces a spray (in
the case of an electrospray source) or a plume (in the case of a
MALDI ion source), or plurality of sprays or plumes. The spray from
an electrospray ions source initially comprises mostly charged
droplets followed by the progressive formation of ions and
particulates. When a MALDI ion source is used, the plume from a
MALDI ion source typically comprises a mixture of ions and
particulates where the particulates can be hydrated or simply
charged or neutral particles (depending on the degree of thermal
heating from the MALDI laser). Regardless of the ion source type,
the presence of either undesolvated droplets or particulates may
degrade the quality of the ion stream and interfere with the
transmission of the ions through the aperture 4 of the mass
spectrometer 32. As described below, the ion interface of the
present invention enables the removal of the undesirable
particulates from the ion stream before the ions enter the vacuum
chamber containing the mass spectrometer.
For simplicity of description, the following description describes
an embodiment in which the ion source is an electrospray source. It
will be appreciated, however, that the ion interface of the
invention is also effective in removing undesirable charged
particulates from the plumes of ions generated by a MALDI source.
Still referring to FIG. 1, a spray 2 from an electrospray source
comprises a mixture of ions, droplets and particulates directed
towards a curtain flow region 17. The curtain flow region 17 is
defined by the region in front of the inlet 24 to the entrance cell
27. The curtain plate 5 has an opening 6 positioned centered on the
line defined by the axis 20, and curtain gas 7 supplied by gas
source 61 flows in the curtain flow region 17 between the orifice 6
and the inlet 24 of the entrance cell 27. Depending on the type of
ion source used, the gas source 61 can be adjusted to supply a
range of flow rates including no flow at all.
The curtain plate 5 can take the form of a conical surface as in
FIG. 1, or a flat surface as shown in FIG. 2, a ring, or any other
suitable configuration for directing the curtain gas 7 to the
curtain flow region 17. In FIGS. 1 and 2, like numerals represent
the like elements, but for clarity, some of the reference numbers
have been omitted. Some of the curtain gas 7 will tend to flow into
the inlet 24 as well as out through the orifice 6 in an opposing
direction to the spray 2. When the spray 2 encounters the curtain
gas 7, turbulent mixing occurs whereby the droplets desolvate and
release ions. The curtain plate 5 and the curtain gas 7 can be
heated to an elevated temperature (typically from 30 to 500.degree.
C.) to facilitate the desolvation process. As the ions continue to
travel in a direction towards the mass spectrometer 32, neutral
particulates and residual neutral droplets 14, collide with the
curtain gas 7 or the general background gas and are prevented from
entering the inlet 24. Thus, the neutral particulates and residual
neutral droplets are discriminated from the remainder of the
plume.
The ions, the charged particles, the residual charged droplets, and
a portion of the curtain gas 7 flow into an entrance cell 27, which
is located within a heated chamber 26, having a bore 58. When an
electrospray source is used, the entrance cell is heated to help
desolvate the charged droplets from the electrospray source. For
this reason, the entrance cell 27 is also referred to as the
desolvation cell in the following description. Secondary
desolvation occurs, a result of the heated chamber 26 convectively
transferring heat to the residual charged droplets. Ions are
released from the desolvated droplets but those charged droplets
that form charged particulates are permitted to flow through the
desolvation cell 27. Subsequently, the ions and the charged
particulates emerging from the heated chamber exit 25 travel into a
second particle discriminator cell 30, located between the heated
chamber exit 25 and the partition 3 and confined by the spacer 29
in the radial direction. The inner diameter of the spacer 29 is
greater than the internal bore 58 of the heated chamber 26, which
is greater than the aperture 4 of the partition 3. Typically, the
aperture 4 has diameter between 0.10 to 1.0 mm with wall thickness
between 0.5 to 1.0 mm, the spacer 29 has diameter between 2 to 20
mm and the bore 58 of the heated chamber 26 has diameter between
0.75-3 mm. The curtain plate 5, the heated chamber 26, the spacer
29 and the partition 3 are electrically isolated from each other by
appropriately known methods, having one pole (depending on the
polarity of the ions desired) of voltage sources 40, 41, 42 and 43
connected to them respectively. As is conventional, the voltage
sources 40, 41, 42 and 43, are configured for direct current,
alternating current, RF voltage, grounding or any combination
thereof. The spacer 29 can be fabricated from a non-conductive
material such as ceramic, in which no potential is applied. As
indicated previously, the pressure between the partition 3 and ion
source 1 is substantially atmospheric and as such, the mating
surface between the heated chamber 26 to the spacer 29 and the
mating surfaces between the spacer 29 to the partition 3 do not
require vacuum tight seals. However, because a net flow, comprising
of the spray 2 and a portion of the curtain gas 7, in the direction
from the ion source 1 to the aperture 4 is desired, a substantially
leak free seal is preferable. The net flow at any point between the
ion source 1 and aperture 4 may be supplemented by an additional
source of gas, if the gas streamlines 18, described below, remain
laminar.
In operation, the electric field and the gas flow dynamics that are
present in the particle discriminator cell 30 create a charged
particle discrimination effect that reduces the amount of
undesirable charged particles entering the aperture 4. To better
understand this process, a discussion of the gas flow dynamics and
the electric field effects are independently presented by the
following.
First, to illustrate the gas flow dynamics, reference is made to
FIG. 3, of which shows a sectional view taken along the central
axis 20 showing the gas flow streamlines from a 2-dimensional
computational fluid dynamic (CFD) modeling of the particle
discriminator cell 30 including a portion of the desolvation cell
27. The vertical axis 34 is a measure of the distance (in mm) from
the central axis 20 while the gradations on the horizontal axis 35
are measured from the inlet 24 of the heated chamber 26. The
diameter of the aperture 4 is about 0.25 mm and the vacuum pressure
in chamber 10 is between 1-5 mbarr. The streamlines 18 parallel to
the central axis 20, are characterized as having gas flow velocity
between 23 m/s near the central axis 20 and extending out in a
radial direction to about 5 m/s or less near the surface 52 of the
heated chamber 26. Due to the restriction of the aperture 4, the
gas flowing through the aperture 4 is accelerating and the
calculations indicate the instantaneous velocity is above 29 m/s.
The charged particle discriminator (CPD) zone 37 is defined by the
annular zone bounded between the spacer surface 38 and between the
heated chamber exit surface 36 to the aperture partition surface
39. This annular discriminator zone 37 surrounds the central zone
59 (see FIG. 1) through which the bulk of the ion stream passes.
Conventionally, as practiced by others, there is a heated capillary
tube for droplet desolvation with either the exit of the capillary
tube positioned directly adjacent to the inlet aperture of the mass
spectrometer, or the capillary tube completely takes the place of
the inlet aperture.
In contrast, the CPD zone 37 serves to create a radial perturbation
or longitudinal discontinuity between the heated chamber exit 25
and the aperture 4, and circulating streamlines 19 are formed. The
circulating streamlines 19 are typically referred to as eddies
having low flow velocities, about 2 m/s, while the streamlines 18
adjacent to the CPD zone 37 tend to converge 31 towards the
aperture 4 at a greater gas flow velocity. Generally, the gas
flowing through the heated chamber 26 and the center of the
particle discriminator cell 30 is laminar, and all the gas flow is
created by the vacuum draw from the mass spectrometer 32. Ions and
charged particulates are distributed across the streamlines 18 with
the large and heavy charged particulates traveling with the
streamlines 18 in a region radially extending beyond line-of-sight
of the aperture 4, breaking free of the streamlines 18 as the
streamlines converge 31, and impact the partition 3 near the
aperture 4. The charged particles nearest to the CPD zone 37 break
free of the converging streamlines and tends to enter the
circulating streamlines 19 of the CPD zone 37 while charged
particles traversing along the central axis 20 in direct
line-of-sight of the aperture, enter the aperture 4. As will be
described later, these line-of-sight charged particles can be
blocked from entering the aperture 4. On the other hand, small
charged particles traversing in the region radially beyond
line-of-sight of the aperture 4 are easily influenced by the gas
flow and will converge 31 through the aperture 4 and pass into the
mass spectrometer 32.
However, with the appropriate electric fields, a number of
surprising effects are taking place, which includes; a) charged
particulates are deflected away from the aperture 4; b) heavy
charged particulates that would normally be impacting adjacent to
the aperture 4 are drawn towards the circulating streamlines 19;
and c) ions continue to traverse through to the aperture 4. The
electric fields thus have the effect of reducing the amount of
deposit collected near the aperture 4 while maintaining ion
transmission to the mass spectrometer.
To illustrate the electric field effects, reference is now made to
FIG. 4, of which shows the electric field modeling for the region
described in FIG. 3. In this model, the potential on the heated
chamber 26 is set at +500 volts, the potential on the partition 3
is set at +40 volts and the spacer 29 has a conductive material
inset (not shown) also set at +40 volts. As previously discussed,
the spacer 29 can be appropriately constructed entirely of an
electrically insulating material such as ceramic where no voltage
is applied. The electric field created by the voltage distribution
is represented by the different lines. For example, the lines 45,
46 and 47 are equal potential lines (equipotentials), representing
approximately 400, 300 and 150 volts respectively. The
equipotentials indicate that the electric field diverges away from
the central axis 20 towards a direction indicated by the arrow 48.
Charged particles traversing in the direction from the heated
chamber exit 25 towards the aperture 4 will tend to be diverted in
the direction of the arrow 48. FIG. 5 is a representation of the
particle discrimination evident on the partition 3. A sample of
cytochrome c digest was used for the analysis. There are three
distinct regions of deposit on the partition 3 located around the
aperture 4. The first region 49 is comprised of a deposit of heme
groups from the cytochrome c digest. This deposit, referred to as a
primary deposit, may be extensively dispersed as the potential
difference between the heated chamber 26 and partition 3 is
increased. For instance, if the heated chamber 26 is operated at
the same potential as the partition 3, the diameter of this deposit
is typically about 680 .mu.m, and if the potential difference is
increased to 400 V, the diameter of this deposit is typically about
790 .mu.m. The increased dispersion of the deposit with electric
field has no effect on the protein ion count rate, which indicates
that the ions are unperturbed, and are swept along with the laminar
gas flow towards the aperture 4.
The second region 50 of interest corresponds to a clear area
surrounding the primary deposit. This area is generated because
both the gas flow streamlines and the electric field are divergent
relative to the partition 3, causing the charged particles to be
directed away from this area. The final region 51 contains a light
monodisperse layer of material deposited from the edge of the
second region 50, out to the spacer surface 38. This light dusting
occurs as a result of particles that become trapped within the
swirling gas flow of the circulating streamlines 19 in the CPD zone
37. The gas flow properties cause particles within this region to
swirl around until they strike the partition 3 and deposit there in
a uniform fashion.
In accordance with an aspect of another embodiment, FIG. 6 shows a
blocking member 57 located on the central axis 20, between the
heated chamber exit 25 and the exit 55 of the spacer 29 to provide
charged particle discrimination by eliminating the direct
line-of-sight for particles traversing along the axis 20. The
diameter of the blocking member 57 is smaller than the inner
diameter of the heated chamber 26 and larger than the diameter of
the aperture 4. For example, a 300 .mu.m blocking member 57 is
suitable with a 2 mm heated chamber 26 bore. Generally, the
blocking member 57 is larger than the diameter of the aperture 4,
but the size can vary depending on the gas flow conditions passing
through the heated chamber 26 and through the spacer 29. More
specifically, the diameter and the positioning of the blocking
member 57 with respect to the aperture 4, is chosen such that flow
streamlines 18 upstream and flow streamlines 62 downstream of the
blocking member 57 remain laminar, see FIG. 7, where like numerals
represent like elements in FIG. 3. In addition, the streamlines 62
downstream of the blocking member 57 should have sufficiently
converged back towards the central axis 20 such that the
streamlines 62 will further converge into the aperture 4. It is
preferable to minimize the recirculating streamlines 53 located
downstream of the blocking member 57. Therefore, positioning the
blocking member to provide the above conditions, larger particles
will not be carried around the blocking member 57 by the gas flow.
Consequently, the larger particles will impact and deposit onto the
surface of the blocking member 57 while the ions flow around and
enter the aperture 4. The blocking member 57 can be an electrical
insulator or can be an electrically conductive element having one
pole (depending on the polarity of the ions desired) of voltage
sources 60 connected to it to provide an electrostatic field. The
electrostatic field may further help to deflect large charged
particles from the aperture 4.
Additionally, it can be appreciated that the location of blocking
member 57 along the axis 20 is not limited to a position between
the heated chamber exit 25 and the outlet 55 of the spacer 29.
Similar results can be achieved by positioning the blocking member
57 within the bore 58 of the heated chamber 26.
From the above description, particle discrimination is achieved by
a combination of electric field and gas flow contributions present
within the spacer 29. The blocking member 57 removes charged
particulates traversing on axis 20 in the direct line-of-sight with
the aperture 4, while the electric field drives the charged
particulates destined to impact the perimeter of the aperture 4 to
flow into the CPD zone 37. This effect can become more pronounced
by increasing the divergent nature of the electric field between
the heated chamber exit 25 and the partition 3. It is also possible
to vary the bore of the spacer 29 or by changing the shape of the
spacer 29 to provide a larger region of circulating streamlines 19.
For example, as shown in FIG. 8A, for simplicity and brevity, like
parts with the apparatus of FIG. 4 are given the same reference
numbers, the spacer 29 has a diameter for the outlet 55 larger than
the diameter of the inlet 54 and where the transition between the
inlet 54 and outlet 55 is a linear increasing bore. Additionally,
as shown in FIGS. 8B and 8C, again, like reference numerals
indicate like parts of FIG. 4, the inlet 54 to outlet 55
transitions can be shaped with a nonlinear profile to promote
charged particle dispersion.
In a preferred embodiment illustrated in FIG. 1, the spacer 29 is
made of a nonconductive material, electrically isolating the heated
chamber 26 from the partition 3. When the spacer 29 is electrically
conductive, or partially conductive, connected to voltage source 42
and electrically isolated from the heated chamber 26 and from the
partition 3, an electric field in the CPD zone 37 can be created to
provide a radial mobility field. The mobility field can divert
charged particles away from the aperture 4 in the radial direction,
indicated by the arrows 56 in FIG. 1. For example, by applying the
appropriate potential to the spacer surface 38 so that a negative
potential field is created in the CPD zone 37, positively charged
particles are attracted towards the spacer surface 38 and away from
the aperture 4. The magnitude of the negative potential should be
optimized to prevent extraction of high mobility charged ions from
the gas flow stream. Similarly, to detract negatively charged
particles from the aperture 3, a positive potential field can be
created.
Additionally, an inverse mobility chamber can be created by
applying the appropriate potentials to the heated chamber 26,
spacer 29 and partition 3 so that the charged particle's mobility
is directed towards the heated chamber exit surface 36. For
example, the ion source 1 has a potential of +2000 volts, both the
curtain plate 5 and heated chamber 26 have 0 volts, the spacer 29
is non conductive and the partition 3 is supplied with a potential
of +30 volts. This combination of potentials generates an axially
repellant electric field thereby preventing large charged particles
from striking the aperture 3 while not affecting the count rate for
ions. The selection of the potentials in the combination would
depend on the diameters of the bore 58 and the bore 59, and to some
extent the aperture 4. It is conceivable that with the appropriate
combination of potentials, both ions and particulates can be
diverted away from the aperture 4 to provide a convenient method of
interrupting the stream of ions directed to the mass spectrometer.
Similarly, reversing the polarity on the ion source 1 and partition
3 will repel negatively charged particles from the aperture 3. This
is a significant advantage over the prior art because it
substantially improves robustness, by decreasing contamination
through the aperture thereby maintaining the gas conductance limit
into the mass spectrometer.
While preferred embodiments of the invention have been described,
it will be appreciated that changes may be made within the spirit
of the invention and all such changes are intended to be included
in the scope of the claims.
* * * * *